Vaginal anti-infectives

Vaginal anti-infectives are a specific subclass of gynecological pharmaceuticals designed for the treatment and prevention of infections within the vaginal environment, primarily vaginitis and vaginosis. These agents are formulated for local intravaginal administration, allowing high local concentrations of the active agent, minimizing systemic absorption, and maximizing therapeutic efficacy at the site of infection. Vaginal anti-infectives may be antibacterial, antifungal, antiprotozoal, or antiseptic in action, and are available in multiple dosage forms, including creams, gels, tablets, pessaries, and suppositories.

These preparations are essential in treating conditions such as:

• Vulvovaginal candidiasis (VVC)

• Bacterial vaginosis (BV)

• Trichomoniasis

• Mixed infections

• Post-antibiotic vaginal dysbiosis

---

Classification of Vaginal Anti-Infectives by Pathogen Target

Category	Target Organism	Examples of Generic Drugs
Antifungals	Candida albicans, non-albicans spp.	Clotrimazole, Miconazole, Terconazole, Nystatin
Antibacterials	Gardnerella vaginalis, Bacteroides, anaerobes	Metronidazole, Clindamycin, Dequalinium chloride
Antiprotozoals	Trichomonas vaginalis	Metronidazole, Tinidazole
Antiseptics	Mixed flora (non-selective)	Povidone-iodine, Chlorhexidine
Probiotic adjuncts	Restoration of Lactobacillus spp.	Lactobacillus-containing vaginal capsules (supportive only)

Mechanism of Action by Class

• Azole antifungals: Inhibit fungal cytochrome P450 enzymes (especially lanosterol 14α-demethylase), impairing ergosterol synthesis and damaging fungal cell membranes.

• Polyene antifungals (Nystatin): Bind to ergosterol in fungal membranes, forming pores and causing leakage.

• Nitroimidazoles (Metronidazole): Disrupt DNA synthesis in anaerobic organisms and protozoa through reactive intermediates.

• Lincosamides (Clindamycin): Inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit.

• Antiseptics (Povidone-iodine, Dequalinium): Act through oxidative or membrane disruption pathways, targeting a broad spectrum of organisms.

---

Commonly Used Vaginal Anti-Infective Agents (Generic Names and Details)

1. Antifungal Agents

a. Clotrimazole

• Brand: Canesten®, Gyne-Lotrimin®

• Form: Vaginal cream, pessary/tablet

• Dosing: 100 mg for 6 nights, 200 mg for 3 nights, or 500 mg single dose

• Indication: Uncomplicated vulvovaginal candidiasis

• Notes: OTC and prescription; generally well tolerated

b. Miconazole

• Brand: Monistat®

• Form: Cream, suppository

• Dosing: 100 mg x7 days, 200 mg x3 days, 1200 mg single dose

• Notes: Multiple strength options for tailored treatment

c. Terconazole

• Brand: Terazol®

• Form: Vaginal cream (0.4%, 0.8%), suppository (80 mg)

• Indication: Moderate to severe yeast infections

• Dosing: Once daily for 3–7 days

• Prescription only

d. Nystatin

• Brand: Mycostatin®, Nystan®

• Form: Vaginal tablet or pessary

• Mechanism: Polyene antifungal binding to ergosterol

• Use: Especially in non-albicans Candida infections

---

2. Antibacterial/Antiprotozoal Agents

a. Metronidazole

• Brand: Metrogel-Vaginal®, Flagyl® (oral)

• Form: Vaginal gel (0.75%), oral tablet

• Dosing:

  • BV: 5 g intravaginally once daily × 5 days

  • Trichomoniasis: Oral route preferred (2 g single dose or 500 mg BID × 7 days)

• Warnings: Avoid alcohol (disulfiram-like reaction), metallic taste, GI upset

b. Clindamycin

• Brand: Cleocin Vaginal®, Clindesse®

• Form: Cream (2%), ovules (100 mg)

• Dosing: Once daily for 3–7 nights

• Warnings:

  • Weakens latex condoms for 5 days post-treatment

  • May increase risk of Candida superinfection

c. Dequalinium chloride

• Brand: Fluomizin® (EU-available)

• Form: 10 mg vaginal tablet

• Spectrum: Broad, including G. vaginalis, Candida, Trichomonas

• Use: Vaginal infections of mixed etiology; non-antibiotic antiseptic

---

3. Antiseptic Agents

a. Povidone-iodine

• Brand: Betadine Vaginal® (not widely used due to potential mucosal irritation)

• Form: Douche, pessary

• Indication: Non-specific vaginitis, broad-spectrum antiseptic

• Warnings: May impair lactobacilli, irritate mucosa

b. Chlorhexidine acetate

• Form: Vaginal gel (Europe, Asia)

• Use: Vaginitis due to bacteria or yeast

• Note: Rarely used in the US

---

Preferred Agents by Condition

Condition	First-line Vaginal Therapy
Vulvovaginal candidiasis	Clotrimazole, Miconazole, Terconazole, Nystatin
Recurrent candidiasis	Extended course azoles (e.g., 100 mg x 7 days)
Bacterial vaginosis (BV)	Metronidazole gel or Clindamycin cream
Trichomoniasis (if topical used)	Metronidazole gel (oral route still preferred)
Mixed flora vaginitis	Dequalinium chloride

Formulations and Administration

• Vaginal cream: Requires applicator, generally used at bedtime to reduce leakage

• Tablet/pessary: Inserted deep into the vagina using finger or applicator

• Gel: Single-use prefilled applicators offer better hygiene

• Ovules: Solid formulations that melt with body temperature

---

Contraindications

• Known hypersensitivity to the active ingredient

• Clindamycin: History of pseudomembranous colitis

• Metronidazole: First trimester of pregnancy (use with caution)

• Severe mucosal damage or allergy to azole antifungals

---

Precautions

• Use back-up contraception (non-latex) during treatment with creams like Clindamycin

• Avoid vaginal intercourse during treatment course

• Avoid tampon use while using vaginal anti-infectives

• Maintain treatment compliance even if symptoms improve early

---

Adverse Effects

System	Examples
Local	Burning, stinging, itching, erythema
Gastrointestinal	Nausea, vomiting (especially oral metronidazole)
Systemic	Dizziness, metallic taste (metronidazole)
Vaginal flora	Candida superinfection, lactobacillus suppression
Rare	Urticaria, anaphylaxis

Drug Interactions

• Metronidazole + Alcohol: Avoid for 48–72 hours due to disulfiram-like reaction

• Clindamycin: Weakens latex contraceptives

• Azole antifungals: Systemic absorption minimal but may inhibit CYP3A4 in rare cases

• Warfarin: Metronidazole may enhance anticoagulant effect

---

Special Populations

• Pregnancy:

  • Topical azoles are preferred during pregnancy (esp. 7-day course)

  • Oral metronidazole is generally safe in the second/third trimester

  • Clindamycin cream acceptable in second/third trimesters

• Lactation:

  • Most topical antifungals and antibiotics have low systemic absorption and are considered safe

---

Resistance and Recurrence

• Non-albicans Candida spp. (e.g., C. glabrata) may resist azoles → nystatin, boric acid used off-label

• BV recurrence: Common, linked to biofilm formation—may need prolonged metronidazole or probiotic adjunct

• Trichomoniasis: Oral metronidazole preferred due to poor vaginal efficacy

---

Clinical Monitoring

• Symptom resolution (itching, discharge, odor)

• Repeat testing in persistent or recurrent cases

• pH testing for diagnostic aid (BV >4.5; Candida normal pH)

• Microscopy (wet mount, KOH prep) for differential diagnosis

---

Examples of Branded Vaginal Anti-Infective Products

Brand	Generic	Indication
Canesten®	Clotrimazole	Yeast infection
Monistat®	Miconazole	Vaginal candidiasis
Metrogel-Vaginal®	Metronidazole	Bacterial vaginosis
Cleocin Vaginal®	Clindamycin	Bacterial vaginosis
Terazol®	Terconazole	Yeast infection
Fluomizin®	Dequalinium chloride	Mixed vaginitis
Mycostatin®	Nystatin	Candidiasis (non-albicans)
Betadine® Vaginal	Povidone-iodine	Antiseptic cleansing (limited use)